Effects of gaseous anesthetics and ultrashort and short-acting barbiturates on human blood platelet free cytosolic calcium: relevance to their effects on platelet aggregation

1992 ◽  
Vol 70 (8) ◽  
pp. 1161-1166 ◽  
Author(s):  
R. B. Philp ◽  
P. Arora ◽  
D. J. McIver
Keyword(s):  
Nitrous Oxide ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Cytosolic Calcium ◽  
Common Mechanism ◽  
Myristate Acetate ◽  
Elevated Pressures ◽  
Human Blood Platelet ◽  
High Doses

The effects of elevated pressures (to 6 atmospheres absolute (ATA)) of nitrous oxide (N2O) and of xenon (Xe), and barbiturates on platelet free cytosolic calcium ([Ca2+]i) and platelet aggregation were studied. N2O inhibited the ADP-induced rise in [Ca2+]i whereas Xe had no effect. Neither affected basal levels. Pentobarbital and methohexital had little effect on basal or stimulated levels in the presence or "absence" of extracellular Ca2+; but both, at concentrations > 10−4 M, inhibited platelet aggregation induced by adenosine diphosphate. Thiopental increased basal and stimulated [Ca2+]i when extracellular Ca2+ was present, but not when it was absent, and displayed a bimodal effect with low and high doses being more active than intermediate ones. It also potentiated aggregation. Methitural displayed similar, but nonsignificant, effects. These patterns held for all agents whether or not acetylsalicylic acid was present. Pentobarbital and methohexital inhibited phorbol myristate acetate aggregation in low extracellular calcium and no potentiation was seen with thiopental. In the absence of extracellular Ca2+, no potentiation was observed in stimulated platelets. Potentiation of aggregation previously reported for Xe does not involve increased Ca2+ uptake and did not occur in the absence of extracellular Ca2+. A common mechanism of action for these agents cannot be inferred from their effects on platelet aggregation or [Ca2+]i, as their pharmacological profiles differ markedly. It is evident that their inhibitory properties in this cell are not dependent on extracellular Ca2+, whereas the potentiation observed with pentobarbital, and formerly with Xe, is so dependent.Key words: platelets, aggregation, calcium, anesthetics, narcotic gases.

Platelet Aggregation in Whole Blood: The Role of Thromboxane A2 and Adenosine Diphosphate

1985 ◽  
Vol 54 (03) ◽  
pp. 612-616 ◽  
Author(s):  
A J Carter ◽  
S Heptinstall
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Thromboxane B2 ◽  
Lipoxygenase Inhibitor ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

SummaryThe platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined.Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis - aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor) - did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

Opposite Effect of Lysine on Platelet Aggregation Induced by Arachidonate and by Other Aggregants

1982 ◽  
Vol 48 (01) ◽  
pp. 078-083 ◽  
Author(s):  
C Ts'ao ◽  
S J Hart ◽  
D V Krajewski ◽  
P G Sorensen
Keyword(s):  
Platelet Aggregation ◽  
Secondary Phase ◽  
Aminocaproic Acid ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Primary Phase ◽  
High Doses ◽  
The Many ◽  
Induced Aggregation

SummaryEarlier, we found that ε-aminocaproic acid (EACA) inhibited human platelet aggregation induced by adenosine diphosphate (ADP) and collagen, but not aggregation by arachidonic acid (AA). Since EACA is structurally similar to lysine, yet these two agents exhibit vast difference in their antifibrinolytic activities, we chose to study the effect of lysine on platelet aggregation. We used L-lysine-HCl in these studies because of its high solubility in aqueous solutions while causing no change in pH when added to human plasma. With lysine, we repeatedly found inhibition of ADP-, collagen- and ristocetin-induced aggregation, but potentiation of AA-induced aggregation. Both the inhibitory and potentiation effects were dose-dependent. Low doses of lysine inhibited the secondary phase of aggregation; high doses of it also inhibited the primary phase of aggregation. Potentiation of AA-induced aggregation was accompanied by increased release of serotonin and formation of malondialdehyde. These effects were not confined to human platelets; rat platelets were similarly affected. Platelets, exposed to lysine and then washed and resuspended in an artificial medium not containing lysine, remained hypersensitive to AA, but no longer showed decreased aggregation by collagen. Comparing the effects of lysine with equimolar concentrations of sucrose, EACA, and α-amino-n-butyric acid, we attribute the potent inhibitory effect of lysine to either the excess positive charge or H+ and C1− ions. The -NH2 group on the α-carbon on lysine appears to be the determining factor for the potentiation effect; the effect seems to be exerted on the cyclooxygenase level of AA metabolism. Lysine and other chemicals with platelet-affecting properties similar to lysine may be used as a tool for the study of the many aspects of a platelet aggregation reaction.

Measurement of Whole Blood Platelet Aggregation by Multiplate® Aggregometry Before and during Aspirin Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3895-3895
Author(s):  
Susanne B. Pedersen ◽  
Steen D. Kristensen ◽  
Anne-Mette Hvas
Keyword(s):  
Platelet Aggregation ◽  
Roc Curve ◽  
Area Under The Curve ◽  
Reference Method ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Impedance Method ◽  
Healthy Individuals ◽  
Operating Characteristics ◽  
Normal Platelet

Abstract The inhibition of platelet aggregation by aspirin (ASA) is fundamental in treatment of ischemic heart disease (IHD). Several studies report findings of normal platelet aggregation despite ASA treatment in some individuals, referred to as ASA resistance (AR). It has been hypothesized that AR increases the risk of a future ischemic event. We evaluated a new impedance method for measurement of platelet aggregation, Multiplate® aggregometry (MA), and compared this method to light aggregometry ad modum Born (OPA), with reference to repeatability and detection of AR. Blood samples from 43 IHD patients and 21 healthy individuals treated with ASA 75 mg daily were analyzed in duplicate by MA and OPA on 4 consecutive days. An additional blood sample was obtained prior to ASA treatment in the group of healthy individuals. Compliance was confirmed by measurements of thromboxane B2 in serum. MA was performed with arachidonic acid (AA) in concentrations of 0.25 mM, 0.50 mM and 0.75 mM, and with adenosine diphosphate (ADP) in concentrations of 7.5 μM and 15 μM. OPA was performed with AA-concentrations of 0.5 mM, 1.0 mM and 1.5 mM, and with ADP-concentrations of 5 μM and 10 μM. Table 1. Area under the curve (AUC) measured by MA in patients and in healthy individuals before and during ASA treatment. Agonist AUC, aggregation units · min Healthy Before ASA HealthyDuring ASA PatientsDuring ASA Median Range Median Range Median Range AA, mM 0.25 520 402–999 38 12–83 41 8–110 0.50 574 461–976 51 20–112 56 17–187 0.75 551 434–889 68 21–333 98 18–418 ADP, μM 7.5 474 272–859 422 195–816 472 126–720 15 503 328–922 479 262–995 525 172–834 In healthy individuals, the AA-induced AUC was reduced significantly by ASA at all concentrations (88–93%, p=0.0001). The reduction of AUC was small and insignificant when using ADP (5–11%, p≥0.06). There was a trend towards a higher median AUC measured in patients than in healthy individuals during ASA (p=0.07). Table 2. Coefficients of variation (CV) of double measurements determined by MA and OPA in healthy individuals prior to ASA treatment and during ASA treatment. AA, mM MA AA, mM OPA CVBefore ASA, % CVDuring ASA, % CVBefore ASA, % CVDuring ASA, % 0.25 8 46 0.5 48 25 0.50 10 40 1.0 5 20 0.75 12 41 1.5 5 21 The CV of OPA was generally lower. The reference method was OPA with AA 1.0 mM and AR was defined as a residual platelet aggregation ≥ 20%. According to this definition 7 participants (16%) had AR. A receiver operating characteristics (ROC) analysis showed a sensitivity of MA using AA 0.75 mM of 100% at an AUC cut-point of 94 aggregation units (AU) · min, 71% at 135 AU · min and 29% at 212 AU · min. The specificity was 60, 81 and 93%, respectively. The area under the ROC-curve was 0.79 (95% CI 0.66–0.92). In conclusion, the large ASA-induced reduction in AUC of healthy individuals indicated that MA measures the effect of ASA efficiently when using AA. ADP seems less suitable, as the AUC was only slightly reduced by ASA. The CV of MA was high during ASA treatment, indicating that platelet aggregation during ASA was low and difficult to measure precisely with MA. The area under the ROC-curve was moderately satisfying, but of uncertain correctness due to the rather small number of observations.

Identification of a Glycoprotein III a Dimer in Polyacrylamide Gel Separations of Human Platelet Membranes

1987 ◽  
Vol 58 (02) ◽  
pp. 694-697 ◽  
Author(s):  
J J Calvete ◽  
J L McGregor ◽  
G Rivas ◽  
J González-Rodríguez
Keyword(s):  
Platelet Aggregation ◽  
Molecular Mass ◽  
Blood Platelet ◽  
High Molecular Mass ◽  
Two Dimensional ◽  
Membrane Glycoproteins ◽  
Human Blood Platelet ◽  
Severe Reduction ◽  
Glycoprotein Iiia ◽  
Peptide Map

SummaryMembrane glycoproteins IIb and IIIa play a major role in human blood platelet aggregation. The absence or the severe reduction of these two membrane glycoproteins, as observed in platelets of Glanzmann’s thrombasthenic patients, is related to a lack of platelet aggregation. Separation of Glanzmann’s thrombasthenic platelet samples by two-dimensional polyacrylamide O’Farrell gels show the absence of a high and several low molecular mass glycoproteins, in addition to the loss of glycoproteins IIb and IIIa (McGregor J. L. et al. Eur. J. Biochem. 1981; 116: 379-388). The aim of this study was to identify the nature of the high molecular mass component, absent in thrombasthenic platelets. A high molecular mass glycoprotein (200 kDa), present in two-dimensional SDS-polyacrylamide O-Farrell gel separations, was recognized by a monoclonal antibody (MP37) directed against glycoprotein IIIa. Moreover, the tryptic peptide map of this high molecular mass glycoprotein was nearly identical to that of glycoprotein IIIa. These results indicate that this high molecular mass glycoprotein present in SDS-polyacrylamide gels is a dimer of glycoprotein IIIa. This work raises the possibility that the high molecular mass glycoprotein, absent in two-dimensional O’Farrell gel separations of thrombasthenic platelets, is a dimer of glycoprotein IIIa.

Effects of Lead Acetate on Platelet Aggregation, Ultrastructure and Serotonin Release

1971 ◽  
Vol 26 (03) ◽  
pp. 455-466 ◽  
Author(s):  
R. B Davis ◽  
G. C Holtz
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Lead Acetate ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Human Platelets ◽  
Serotonin Release ◽  
Aggregation Of Platelets

SummaryThe effects of lead on blood platelet function and ultrastructure have been investigated. Lead acetate was injected intravenously in 27 rats and was added to rat and human platelet rich plasma in vitro. In vitro studies showed that concentrations of 2.5 × 10-3 M lead acetate reduced or blocked aggregation of rat and human platelets by adenosine diphosphate, collagen, and thrombin. Radioactive serotonin release from human platelets was inhibited by 10-4 M lead acetate. One hour after the injection of lead, platelet aggregation by thrombin was reduced, but platelet aggregation by adenosine diphosphate and collagen showed little change. Three days after lead, aggregation of platelets by collagen and thrombin was blocked and aggregation by adenosine diphosphate reduced. Thrombocytopenia was present 4 days after intravenous lead acetate. Electron micrographs of platelets showed that the mean number of mitochondria per platelet was increased, whereas alpha granules were reduced. Dense bodies were not significantly changed. Lead acetate affects platelet function in concentrations reported in human bone marrow in lead poisoning, and may relate to the binding of free sulfhydryl groups by lead.

Platelet Aggregation in Whole Blood Determined Using the Ultra-Flo 100 Platelet Counter

1982 ◽  
Vol 48 (03) ◽  
pp. 327-329 ◽  
Author(s):  
S C Fox ◽  
M Burgess-Wilson ◽  
S Heptinstall ◽  
J R A Mitchell
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Blood Platelet

SummaryThe Ultra-Flo 100 Whole Blood Platelet Counter has proved a useful tool for measuring platelet aggregation in whole blood, the extent of aggregation being deduced from the number of single platelets that remain. The technique has allowed us to show that platelets aggregate spontaneously in citrated blood and in heparinized blood but not in whole blood collected into EDTA. The aggregation occurs during storage but its rate is enhanced by stirring and it occurs more readily when the whole blood has been exposed to plastic rather than glass. It occurs much more readily in whole blood from some individuals than from others and the process may involve adenosine diphosphate (ADP). The rate of aggregation in whole blood is enhanced by several aggregating agents including collagen, ADP and sodium arachidonate which are more usually studied in platelet-rich plasma.

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